Molecular determinants of behavioral changes induced by neonatal ketamine and dexmedetomidine application.


Journal of neural transmission (Vienna, Austria : 1996), vol.126, no.12, pp.1577-1588, 2019 (Journal Indexed in SCI Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 126 Issue: 12
  • Publication Date: 2019
  • Doi Number: 10.1007/s00702-019-02081-1
  • Title of Journal : Journal of neural transmission (Vienna, Austria : 1996)
  • Page Numbers: pp.1577-1588


Ketamine (KET), an anesthetic, analgesic, and a sedative N-methyl-d-aspartate (NMDA) receptor antagonist agent, exposure during neonatal period may lead to learning impairment, behavioral abnormalities, and cognitive decline in the later years of life. In recent studies, it has been reported that sedative-acting alpha 2 agonist dexmedetomidine (DEX), which is commonly used in clinical practice with KET, has neuroprotective effects and prevents the undesirable effects of anesthesia. To elucidate the underlying mechanisms of these actions, we investigated the interaction between NMDA receptors alpha(2) adrenoceptor and adulthood behaviors in neonatally KET and/or DEX administrated mice. Balb/c male mice were administrated with saline, KET (75 mg/kg), DEX (10 mu g/kg), or KET + DEX (75 mg/kg + 10 mu g/kg) on postnatal day 7. During adulthood (8-10 weeks old) mice were subjected to elevated plus maze, open field, and Morris water maze tests. After behavioral tests, hippocampus samples were extracted for mRNA expression studies of NMDAR subunits (GluN1, GluN2A, and GluN2B) and alpha(2) adrenoceptor subunits (alpha(2A), alpha(2B), and alpha(2C)) by real-time PCR. Ketamine increased horizontal and vertical locomotor activity (p < 0.01) and impaired spatial learning-memory (p < 0.05). DEX increased anxiety-like behavior (p < 0.01), but did not affect spatial learning-memory and locomotor activity. KET + DEX impaired spatial learning-memory (p < 0.01), increased horizontal locomotor activity (p < 0.01), and anxiety-like behavior (p < 0.05). Our study implies that DEX cannot prevent the adverse effects of KET, on spatial learning-memory, and locomotor activity. In addition to this, it can be thought that during brain development, there is an interaction between NMDAR and alpha(2) adrenoceptor systems.